Abstract PD04-09: Multiple Biomarker Expression in Circulating Tumor Cells from Metastatic Breast Cancer Patients

Abstract

Abstract Background: Numeration of circulating tumor cells, CTCs, from metastatic breast cancer (MBC) patients (pts) is predictive of outcome. Biomarker characterization of CTCs may be a useful adjunctive guide for personalized targeted and systemic treatment (Rx) selection. Method: A multimarker assay was used to simultaneously quantify expression of HER2, ER and ERCC1. A fast laser scanning instrument was used for sensitive location of CTCs on large glass substrates. CTCs are identified using automated digital microscopy by morphology, the presence of cytokeratin and a nucleus, and the absence of CD45. At the COHCC pts with newly diagnosed/progressing MBC were accrued. Blood samples (10 ml) were procured prior to initiating systemic Rx and at subsequent 3 month intervals and sent to PARC for analysis. Cell lines with expression of each marker were used for normalization of the cell intensities. Sample scores were derived from the percentage of CTCs expressing the marker and the average expression level. Results: The multiple-marker assay was done on CTCs at repeat time points and results were compared to findings from the original primary BCs (P) and biopsied metastases (M) in 30 and 20 MBC pts respectively. While P and M tissue scores were concordant for HER2, the CTC score was discordant in 58% of the samples; HER2 expression changed during Rx in 19% of pts. While the status for ERCC1 was discordant between P and M tissue in 13% of the pts, CTCs scores were discordant with P and M tumors in 63% and 67% of the patients respectively, and CTC expression status changed during Rx in 15% and 7% of pts respectively. While the status for ER was discordant between P and M tissue in 15% of the pts, CTC scores were discordant from the P and M tumors in 42% and 71% of pts respectively, and CTC ER status changed in 7% and 17% respectively of pts during Rx. Conclusions: Significant discordances in expression level of ER, HER2 andERCC 1 was observed between CTCs, and both primary and metastatic BC tissue. Changes in CTC expression patterns were also observed during the course of Rx for all three markers. Correlation of CTC biomarker expression patterns and changes with response to Rx therapy is ongoing to validate medical significance. Multimarker testing may ultimately lead to improvements in personalized Rx for pts with MBC. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD04-09.